1. Field of the Invention
The present invention relates, in general, to hepatitis A viruses. In particular, the present invention relates to cynomolgus monkey hepatitis A viruses and vaccines containing same.
2. Background Information
Humans have been considered the natural host for hepatitis A virus (HAV), although nonhuman primates can be infected experimentally (Dienstag, J. L., et al. (1975) Journal of Infectious Diseases 132, 532-545). Human HAV is a single serotype and different isolates have shown a high degree of nucleotide and amino acid conservation. HAV infections in wild-caught Panamanian owl monkeys (Aotus trivireatus) have been thought to be caused by a host-specific HAV, designated PA 21 (Brown, E. A., et al. (1989) Journal of Virology 63, 4932-4937). Although the nucleic acid sequence of the capsid region of PA 21 differs by more than 17% from most of the sequenced human HAV isolates, this genotype has now been identified in patients with hepatitis A (Jansen, R. W., et al, (1990) Proc. Natl. Acad. Sci. USA 87, 2867-2871; Robertson, B. H., et al. (1991) Journal of Infectious Diseases 163, 286-292).
Antibody to HAV has been detected in newly captured cynomolgus macaques (Macaca fascicularis) and was thought to be the result of infection with human HAV (Burke, D. S., et al. (1984) American Journal of Tropical Medicine and Hygiene 33, 940-944). The present invention provides the sequence of the capsid region of HAV isolated from cynomolgus monkeys (cyno-HAV) and demonstrates that it is divergent from other HAV isolates and contains significant amino acid changes within the putative immunodominant site.